The approval was based on an international, multicenter, randomized (2:1), phase 2 study comparing every three-week intravenous infusions of siltuximab and best supportive care (BSC) to placebo and BSC. The trial enrolled 79 patients and randomly allocated 53 patients to the siltuximab arm plus BSC and 26 patients randomized to the placebo arm plus BSC. Siltuximab was administered every three weeks as an intravenous infusion at a dose of 11 mg/kg.

The trial met its primary endpoint of “durable tumor and symptomatic response” defined as a tumor response (partial and complete responses) assessed by independent review and complete resolution or stabilization of MCD symptoms. Thirty-four MCD related symptoms were prospectively identified and collected and graded (NCI-CTAEv4) by the investigator. A durable response was defined as a tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. The durable tumor and symptomatic response rates were 34% (18/53) versus 0% (0/26) for the siltuximab and placebo groups, respectively [(95% CI: 11.1, 54.8) p=0.0012].

Additional supportive pre-specified endpoints included tumor response, time-to-treatment failure and an increase in hemoglobin of at least 1.5 grams/dL at week 13 in patients who were anemic at study entry. Tumor response rates were 38% versus 4% for the siltuximab and placebo groups, respectively (p<0.05). The median time- to- treatment failure, with a median follow-up of 422 days, was not reached in the siltuximab arm and was 134 days in the placebo arm [HR 0.418 (95% CI: 0.21 to 0.82) p <0.05]. An increase in the level of hemoglobin described above was observed in 19 patients on the siltuximab arm and no patients on the placebo arm [(95% CI: 28.3, 85.1) p <0.05].

The common adverse reactions (>10% compared to placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

The recommended dose and schedule for siltuximab is 11 mg/kg dose given over 1 hour by intravenous infusion every 3 weeks.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).